Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model

Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular pathogenesis in brain malignancies could inform the development of staged therapies for these highly pharmaco-resistant epilepsies. Studies in immunodeficient xenograft models have identified local interneuron loss and excess glial glutamate release as chief contributors to network disinhibition, but how hyperexcitability in the peritumoral microenvironment evolves in an immunocompetent brain is unclear. We generated gliomas in WT mice via in utero deletion of key tumor suppressor genes and serially monitored cortical epileptogenesis during tumor infiltration with in vivo electrophysiology and GCAMP7 calcium imaging, revealing a reproducible progression from hyperexcitability to convulsive seizures. Long before seizures, coincident with loss of inhibitory cells and their protective scaffolding, gain of glial glutamate antiporter xCT expression, and reactive astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later extended far beyond tumor boundaries. Hitherto unrecognized episodes of cortical spreading depolarization that arose frequently from the peritumoral region may provide a mechanism for transient neurological deficits. Early blockade of glial xCT activity inhibited later seizures, and genomic reduction of host brain excitability by deleting MapT suppressed molecular markers of epileptogenesis and seizures. O...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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ConclusionOur results suggest that SDT with FL and low-intensity FUS is effective in inhibiting the growth of ectopic malignant gliomas in rats. The selective FL extravasation and accumulation in the tumor areas where the blood –brain barrier is damaged suggests the tumor-specificity of the treatment. The possibility to use this treatment in intracranial models and in human gliomas will have to be explored in further studies.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
This study is assessed an optimized ferroptosis gene panel for glioma treatment. MATERIAL AND METHODS We obtained 45 reports on ferroptosis-related proteins in PubMed and conducted a statistical test of the patients' overall survival (OS) in the TCGA GBMLGG and CGGA databases. The statistically significant genes were screened for an optimal panel, followed by GO and KEGG analysis and evaluated its correlation with known prognostic factors of glioma, including IDH1 mutation, methylated MGMT, tumor purity, 1p/19q LOH, and methionine cycle. RESULTS Eight genes panel (ALOX5, CISD1, FTL, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) ...
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
AbstractDiffuse glioma is the deadliest form of brain cancer, and the median survival of grade IV glioma (glioblastoma, GBM) is no more than 2  years even with maximal surgical resection followed by radiotherapy and chemotherapy, which are now the standard of care for GBM. Glioma shares common characteristics with most malignant tumours, such as invasiveness, rapid progression, resistance to various therapies and inevitable recurrence, wh ile it also has its own unique features, such as high aggressiveness and immunotherapy resistance, which can be, respectively, attributed to epithelial-mesenchymal transition (EMT) a...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
Pediatric diffuse intrinsic pontine glioma (DIPG) represents one of the most devastating and lethal brain tumors in children with a median survival of 12 months. The high mortality rate can be explained by the...
Source: Cerebrospinal Fluid Research - Category: Neurology Authors: Tags: Research Source Type: research
CONCLUSION: PP and TN occur in clinically distinct patient populations and exhibit differences in spatial radiographic pattern. Increased familiarity with both conditions and their unique features will improve patient management and may avoid unnecessary surgical procedures. IMPLICATIONS FOR PRACTICE: Pseudoprogression (PP) and treatment-induced brain tissue necrosis (TN) are challenging treatment-related effects mimicking tumor progression in patients with brain cancer. Affected patients frequently require surgery to guide management. PP and TN remain arbitrarily defined and insufficiently characterized. Lack of clea...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
ConclusionsThis original human BBTB model allows a better understanding of the influence of DIPG on the BBTB ECs phenotype. Our data reveal that the chemoresistance described for DIPG does not come from the development of a “super BBB”. These results, validated by the absence of modification of drug transport through the BBTB ECs, point out the importance of understanding the implication of the different protagonists in the pathology to have a chance to significantly improve treatment efficiency.
Source: Fluids and Barriers of the CNS - Category: Neuroscience Source Type: research
This study aimed to investigate the association of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations with cognitive functions of glioma and meningioma patients. Methods: 177 brain tumor patients awaiting for brain tumor surgery participated in the study. Patients were assessed preoperatively, using neuropsychological tests for verbal memory, psychomotor speed, mental flexibility, and verbal fluency. The functional status of patients was evaluated using the Karnofsky Performance Index. Blood samples were drawn for evaluation of serum hsCRP and NT-...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Abstract According to the WHO classification criteria, the most common intracranial tumor gliomas can be divided into four grades based on their symptoms. Among them, Grade Ⅰ and Grade II are low-grade gliomas, and Grade III and Grade IV are high-grade gliomas. Because gliomas have a high lethal rate, they have received widespread attention in the medical field. Based on these circumstances, a rapid and facile surface enhanced Raman scattering (SERS) method using silver nano particle-decorated silver nanorod (AgNPs@AgNR) as substrates were developed for the discrimination of gliomas. Compared with SERS-active si...
Source: Talanta - Category: Chemistry Authors: Tags: Talanta Source Type: research
Source: Clinical Trials And Noteworthy Treatments For Brain Tumors - Category: Cancer & Oncology Source Type: clinical trials
;o SR Abstract PURPOSE: The purpose of this study was to assess visual function by visually evoked potentials in adults with orbital and other primary brain tumors affecting the optic pathway. METHODS: In this retrospective case-control series, patients with orbital (intraconal and extraconal) or midline/chiasmatic tumors were included. Visually evoked potentials using pattern-reversal visually evoked potential and flash visually evoked potential stimuli were performed according to the international standards. Outcome measures were visually evoked potential parameters of amplitude (µV) and peak times (m...
Source: European Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Eur J Ophthalmol Source Type: research
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